Neurokinin 1 receptor antagonism requires norepinephrine to increase serotonin function

  title={Neurokinin 1 receptor antagonism requires norepinephrine to increase serotonin function},
  author={Gabriella Gobbi and Tommaso Cassano and Fatiha Radja and Maria Grazia Morgese and Vincenzo Cuomo and Luca Santarelli and Ren{\'e} Hen and Pierre U. Blier},
  journal={European Neuropsychopharmacology},

Evidence for the differential co-localization of neurokinin-1 receptors with 5-HT receptor subtypes in rat forebrain

These experiments demonstrate a high degree of co-localization between NK1Rs and 5-HT1A receptors in cortical and limbic regions of the rat forebrain, and suggest a novel site of interaction betweenNK1R antagonists and the5-HT system.

Neurokinin1 Antagonists Potentiate Antidepressant Properties of Serotonin Reuptake Inhibitors, Yet Blunt Their Anxiogenic Actions: A Neurochemical, Electrophysiological, and Behavioral Characterization

Combined NK1 receptor antagonism/5-HT reuptake inhibition may offer advantages in the management of depressed and anxious states: antidepressant properties are reinforced, whereas anxiogenic effects are attenuated.

Sustained Impairment of α2A-Adrenergic Autoreceptor Signaling Mediates Neurochemical and Behavioral Sensitization to Amphetamine

Peripheral CB1 receptor blockade acts as a memory enhancer through an adrenergic-dependent mechanism

A novel peripheral mechanism relevant for the modulation of the formation of persistent non-emotional memory is disclosed, and it is disclosed that intra-hippocampal β-adrenergic blockade prevented AM6545 mnemonic effects.

Mutual independence of 5-HT2 and α1 noradrenergic receptors in mediating deficits in sensorimotor gating

5-HT2 receptors and α1 and β NE receptors may act through independent mechanisms to modulate sensorimotor gating and locomotor activity and modify PPI.

Enhancement of the function of rat serotonin and norepinephrine neurons by sustained vagus nerve stimulation.

Vagus nerve stimulation initially increases the firing activity and pattern of NE neurons and subsequently those of 5-HT neurons, presumably as a cascade effect via alpha(1)-postsynaptic adrenoceptors, and may contribute to the effectiveness of VNS in treatment-resistant depression.

Stress-induced reinstatement of alcohol-seeking in rats is selectively suppressed by the neurokinin 1 (NK1) antagonist L822429

The results provide support for NK1 antagonism as a promising mechanism for pharmacotherapy of alcoholism, acting through suppression of stress-induced craving and relapse.

NK1 (TACR1) Receptor Gene ‘Knockout’ Mouse Phenotype Predicts Genetic Association with ADHD

The proposal that NK1R−/− mice offer a mouse model of ADHD was borne out by human studies, which suggest that DNA sequence changes in and around the TACR1 gene increase susceptibility to this disorder.



Modification of serotonin neuron properties in mice lacking 5-HT1A receptors.

Effect of neurokinin‐1 receptor antagonists on the function of 5‐HT and noradrenaline neurons

Findings suggest that NK1 receptor antagonists affect markedly the NA system via an attenuation of the function of α2-adrenoceptors on the cell body of NA neurons and, consequently, may also modulate 5-HT neurotransmission.

Impact of substance P receptor antagonism on the serotonin and norepinephrine systems: relevance to the antidepressant/anxiolytic response.

Observations strongly suggest that NK1 antagonists could become a new class of antidepressant and anxiolytic agents.

Selective blockade of neurokinin (NK)1 receptors facilitates the activity of adrenergic pathways projecting to frontal cortex and dorsal hippocampus in rats

Findings indicate that selective blockade of NK1 receptors enhances the activity of ascending adrenergic pathways in rats and Adrenergic mechanisms may, thus, be involved in the potential antidepressant and other functional properties ofNK1 receptor antagonists.

Serotonin receptor 1A knockout: an animal model of anxiety-related disorder.

  • S. RambozR. Oosting R. Hen
  • Biology, Psychology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1998
It is demonstrated that mice without 5-HT1A receptors display decreased exploratory activity and increased fear of aversive environments (open or elevated spaces) and suggested that reductions in 5- HT1A receptor density due to genetic defects or environmental stressors might result in heightened anxiety.

Blockade of substance P (neurokinin 1) receptors enhances extracellular serotonin when combined with a selective serotonin reuptake inhibitor: an in vivo microdialysis study in mice

The present findings suggest that NK1 receptor antagonists, when combined with a SSRI, augment 5‐HT release by modulating substance P/5–HT interactions in the dorsal raphe nucleus.

Sustained pharmacological blockade of NK1 substance P receptors causes functional desensitization of dorsal raphe 5‐HT1A autoreceptors in mice

The hypothesis that chronic NK1 receptor blockade induces a functional desensitization of 5‐HT1A autoreceptors similar to that observed with SSRIs is supported.

Long-Term Antidepressant Treatments Result in a Tonic Activation of Forebrain 5-HT1A Receptors

Data indicate that such antidepressant treatments, acting on entirely different primary targets, might alleviate depression by enhancing the tonic activation of forebrain postsynaptic 5-HT1Areceptors.